Journal article
The Null Distribution of the Heterogeneity Lod Score Does Depend on the Assumed Genetic Model for the Trait
Human heredity, Vol.52(4), pp.217-222
11/2001
DOI: 10.1159/000053379
PMID: 11713418
Abstract
It is well known that the asymptotic null distribution of the homogeneity lod score (LOD) does not depend on the genetic model specified in the analysis. When appropriately rescaled, the LOD is asymptotically distributed as 0.5 χ2₀ + 0.5 χ21, regardless of the assumed trait model. However, because locus heterogeneity is a common phenomenon, the heterogeneity lod score (HLOD), rather than the LOD itself, is often used in gene mapping studies. We show here that, in contrast with the LOD, the asymptotic null distribution of the HLOD does depend upon the genetic model assumed in the analysis. In affected sib pair (ASP) data, this distribution can be worked out explicitly as (0.5 – c)χ2₀ + 0.5χ21 + cχ22, where c depends on the assumed trait model. E.g., for a simple dominant model (HLOD/D), c is a function of the disease allele frequency p: for p = 0.01, c = 0.0006; while for p = 0.1, c = 0.059. For a simple recessive model (HLOD/R), c = 0.098 independently of p. This latter (recessive) distribution turns out to be the same as the asymptotic distribution of the MLS statistic under the possible triangle constraint, which is asymptotically equivalent to the HLOD/R. The null distribution of the HLOD/D is close to that of the LOD, because the weight c on the χ22 component is small. These results mean that the cutoff value for a test of size α will tend to be smaller for the HLOD/D than the HLOD/R. For example, the α = 0.0001 cutoff (on the lod scale) for the HLOD/D with p = 0.05 is 3.01, while for the LOD it is 3.00, and for the HLOD/R it is 3.27. For general pedigrees, explicit analytical expression of the null HLOD distribution does not appear possible, but it will still depend on the assumed genetic model.
Details
- Title: Subtitle
- The Null Distribution of the Heterogeneity Lod Score Does Depend on the Assumed Genetic Model for the Trait
- Creators
- Jian Huang - University of IowaVeronica J Vieland
- Resource Type
- Journal article
- Publication Details
- Human heredity, Vol.52(4), pp.217-222
- DOI
- 10.1159/000053379
- PMID
- 11713418
- ISSN
- 0001-5652
- eISSN
- 1423-0062
- Number of pages
- 6
- Language
- English
- Date published
- 11/2001
- Academic Unit
- Statistics and Actuarial Science
- Record Identifier
- 9984257626402771
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